There is widespread demand for proteins which bind to the Fc region of the various types of immunoglobulin G (IgG). These proteins are valuable immunochemical tools for identifying, purifying and quantifying classes and subclasses of Ig from different species. The proteins can also be used to remove IgG from serum and secretions and as immunochemical reagents in a variety of immunoassays. [Jensen, Acta Path. Microbiol. Scand., Vol. 44, p. 421 (1958); Forsgren, J. Immunol. Vol. 97, p. 822 (1966); Kronvall, J. Immunol., Vol. 111(5), p. 1401 (1973). Based on patterns of species IgG reactivity, several distinct groups of such proteins, termed Fc receptors, have been identified [Myhre et al, Immunoglobulin specificities of defined types of steptococcal Ig receptors. In: Basic Concepts of Streptococci and Steptococcal Diseases. Reedbook, Ltd., Chertsey, Surrey (eds. S. E. Holm et al), pp 209-210 (1981)].
The most extensively studied receptor is the Type I found on most Staphylococcus aureus strains. This receptor is presently commercially available as the so-called "Protein A". For a discussion of Protein A and its properties, see Bjork et al, Euro. J. Biochem., Vol. 29, p. 579 (1972); Kronvall, J. Scand. Immunol., Vol. 2, p. 31 (1973); Forsgren et al, Acta, Path. Microbiol. Scand., Vol. 74, p. 466 (1969); Goding, J. Immunol. Methods, Vol. 20, p. 241 (1978); Langone, J. Immunol. Methods, Vol. 51, p. 3 (1982); Kronvall et al, J. Immunol., Vol. 104, p. 140 (1970); Richman et al, J. Immunol., Vol. 28, p. 2300 (1982); Patrick et al, J. Immunol., Forsch, Vol. 153, p. 466 (1977); Lind et al, Scand. J. Immunol., Vol. 4, p. 843 (1975); Coe et al, Molec Immunol., Vol. 18, p. 1007 (1981); Ey et al, Immunochemistry, vol. 15, p. 429 (1978); Langone, Analyt. Biochem., Vol. 93, p. 207 (1979); Boyle et al, J. Natl. Can. Inst., Vol. 62, p. 1537 (1979); Langone, Methods in Enzymology, Vol. 70A (1981); Langone et al, J. Immunol. Methods, Vol. 18, p. 128 (1979); Gee et al, Analyt. Biochem., Vol. 116, p. 524 (1981); Langone, J. Immunol. Methods, Vol. 24, p. 269 (1978); Patrick et al, Immunochemistry, Vol. 15, p. 137 (1978); Langone et al, J. Immunol Methods, Vol. 18, pp. 281-293 (1977); Langone et al, Adv. Immunol., Vol. 32, p. 157 (1982). Protein A has been purified to functional homogeneity from culture supernatants and following enzyme extraction of the Protein A rich Staphylococcus aureus Cowan I strain. The bulk of such preparations contain a major 42,000 dalton protein and a number of other minor protein bands with Fc-reactivities. The usefulness of Protein A is limited only by the range of species, isotypes and subclasses of IgG with which it reacts.
Researchers have also successfully isolated Fc binding molecules from group A streptococcus. This receptor is heterogeneous in size, the predominantly active factor having a molecular weight of 29,500 daltons. The receptor was only obtained when protease inhibitors were included during purification. [Christensen et al, Acta. Path. Microbiol. Scand. (C), Vol. 84, p. 196 (1976); Christensen et al, Acta. Path. Microbiol. Scand. (B), Vol. 82, p. 19 (1974); Havlicek, Exp. Cell Biol., Vol. 46, p. 146 (1978); Christensen et al, Acta. Path. Microbiol. Scand. (C), Vol. 87, p. 257 (1979); Grubb et al, Int. Arch. Allergy Appl. Immunol., Vol. 67, p. 369 (1982)].
Generally, however, attempts to extract and purify streptococcal Fc receptors in any significant amounts have met with only limited success since, unlike Protein A, none of the streptococcal Fc receptors are secreted in significant quantities during culture.
The present invention is predicated on the discovery of a novel factor associated with group C streptococci which is antigenically different from both Protein A and the factor derived from group A streptococci and which selectively reacts with the Fc region of a wider variety of IgG species and subclasses than Protein A.
It is an object of the invention to provide the novel Fc binding factor and immunologically valuable derivatives thereof as well as methods for the derivation, isolation and purification thereof.